Direct technetium-99m labeling of three anticancer monoclonal antibodies: stability, pharmacokinetics and imaging.

Abstract

UNLABELLED:

Monoclonal antibodies (MAbs) directly labeled with 99mTc have been used in a number of clinical immunoscintigraphic investigations. Three anti-cancer MAbs were radiolabeled with 99mTc using a reduction-mediated technique. The stability, biodistribution and in vivo pharmacokinetics were assessed and compared with the same antibodies labeled with 125I.

METHODS:

Immunoreactivity data were obtained by ELISA and RIA. Homogeneity and stability of radiolabeled antibodies (in vitro and in vivo) were measured by size-exclusion, fast protein liquid chromatography and SDS-PAGE. Pre-clinical, in vivo investigations utilized the nude mouse/HEp2 xenograft model, and clinical imaging and pharmacokinetic data were obtained from patients with confirmed or suspected lesions.

RESULTS:

Both 99mTc- and 125I-labeled antibodies were shown to be homogeneous and stable, although 99mTc-labeled antibody fragments were detected by SDS-PAGE. Pharmacokinetic studies in patients revealed a significant difference in the clearance rates between 99mTc- and 125I-labeled antibodies, with those labeled with 99mTc having a shorter biological half-life, indicating that the 99mTc-labeled antibodies may be less stable than the iodinated ones. Nevertheless, specific tumor localization was successfully demonstrated in nude mice bearing a human tumor xenograft using 125I- and 99mTc-labeled H17E2 antibody. Furthermore, in the clinic, using 99mTc-labeled HMFG1 and 1A3, successful imaging was achieved in 12 out of 19 patients with lesions for which these antibodies were specific.

CONCLUSION:

Anticancer MAbs radiolabelled using this reduction-mediated technique are suitable agents for clinical, immunoscintigraphic investigations.

• Authors: C S Gooden, D E Snook, A Maraveyas, G Rowlinson-Busza, A M Peters, A A Epenetos
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 36 Issue 5 Pg. 842-9 (May 1995) ISSN: 0161-5505 [Print] United States
• PMID: 7738662 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• H17E2 monoclonal antibody
• Iodine Radioisotopes
• Technetium

Topics

• Animals
• Antibodies, Monoclonal (pharmacokinetics)
• Humans
• Iodine Radioisotopes (pharmacokinetics)
• Mice
• Mice, Nude
• Neoplasms (diagnostic imaging, immunology)
• Radioimmunodetection
• Technetium (pharmacokinetics)